X linked lymphoproliferative disease (XLP) is an inherited immunodeficiency characterized by increased susceptibility to Epstein-Barr virus (EBV). Following infection with EBV, patients with XLP exhibit a vigorous uncontrolled polyclonal expansion of T and B cells, which may account for a severe or fatal infectious mononucleosis, acquired hypogammaglobulinemia, and/or malignant lymphoma observed in various subjects. The recent identification of a mutated form of the gene, SH2D1 or SAP has provided great insight into our current understanding of XLP and EBV infections. In an effort to define a physiological role for the XLP gene, we examined various normal human tissues for SAP mRNA expression. High levels of SAP mRNA expression was observed in the thymus and lung with modest levels in the spleen and liver and low levels in heart, placenta, muscle, kidney and pancreas. Additional studies using various primary and transformed human lymphocyte populations have demonstrated the differential expression of the SAP protein within the nuclear and cytosolic fractions of these cells during cellular activation. Studies are ongoing to determine the role of SAP in cellular activation and effector functions, which in turn may provide a better understanding of the pathophysiology of XLP.